CN1956737A - Ophthalmic thickening agent - Google Patents
Ophthalmic thickening agent Download PDFInfo
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- CN1956737A CN1956737A CN200580016815.8A CN200580016815A CN1956737A CN 1956737 A CN1956737 A CN 1956737A CN 200580016815 A CN200580016815 A CN 200580016815A CN 1956737 A CN1956737 A CN 1956737A
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- eye
- cellulose
- glucosan
- eye drop
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Abstract
An object of the present invention is to provide an eyedrop which has a relatively low viscosity before instillation but is thickened on the eyeball surface at instillation. The eyedrop containing a viscous agent for ophthalmic use, which comprises a combination of hydroxyethylcellulose and dextran, exhibits a specific and synergistic thickening effect in the coexistence of mucin. Therefore, the eyedrop of the present invention is thickened on the eyeball surface upon contact with mucin in the precorneal tear film at instillation, whereby a desired pharmacological efficacy or refreshing feel can be sustained.
Description
Technical field
The present invention relates to a kind of ophthalmic thickening agent that combines by hydroxyethyl-cellulose and glucosan.In addition, the present invention relates to a kind of eye drop that contains ophthalmic thickening agent, wherein said thickening agent is combined by hydroxyethyl-cellulose and glucosan, contacts by the mucin with the tear film when it is characterized by eye drip viscosity is increased.In addition, the invention still further relates to a kind of tear membrane stabilizer and eye drop eye surface detention promoter that combines by hydroxyethyl-cellulose and glucosan.
Background technology
When eye drop viscosity is higher,, can continue to bring into play desired drug effect or refrigerant sense etc., but the high more eye drip of the viscosity of eye drop is difficult more, also can make the comfort variation in the long-time delay in eye surface.
The eye surface is covered by oil reservoir, water layer and 3 layers of tear film that constitutes of mucin layer.Thereby the mucin layer that is positioned at above-mentioned tear film innermost layer has the effect that makes tear film and eye surface adhering that tear is not poured off, but since the mucin layer cause the tear film unstable unusually the time, in the short time of nictation, can produce the drying nest of so-called dry spot (dryspot), therefore, the xerophthalmia symptom with dry sensation or sense of discomfort appears in eye sometimes.
On the other hand, hydroxyethyl-cellulose is the cellulose derivative with hydroxy ethoxy, is widely used as thickening agent or dispersant.In addition, glucosan is the polysaccharide that obtains by fermentation sucrose, as the thickening agent or the stabilizing agent use of eye drop.
Patent documentation 1 relates to contain the refrigerant invention that changes into the eye drop of branch and thickening agent, as thickening agent, for example records ethyl cellulose, hydroxyethyl-cellulose, glucosan etc.In addition, the pH that patent documentation 2 relates to have the self-preserving ability is the invention of 1.5～3.5 ophthalmic composition, as its additive, records Polyethylene Glycol, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, glucosan etc.
But above-mentioned document does not all make up and cooperates hydroxyethyl-cellulose and glucosan.
Patent documentation 1: the spy opens the 2002-97129 communique
Patent documentation 2: No. 6572849 description of United States Patent (USP)
Summary of the invention
About the viscosity of eye drop,,, therefore can not continue to bring into play desired drug effect or refrigerant sense even then eye drip also can get off from the eye surface current immediately if viscosity is lower.On the other hand, if the viscosity of eyedrop is higher, though then long in the holdup time on eye surface, the high more eye drip of viscosity is difficult more, in addition, has the tendency of comfort variation.Therefore, increase in the eye surface viscosity, can continue to bring into play the desired drug effect or the eye drop of refrigerant sense though people's expectation is developed when the preceding viscosity of a kind of eye drip is lower passes through eye drip.In addition, people also seek to develop a kind of eye drop that can stablize elimination eye dryness sense of tear film or sense of discomfort.
The inventor is conceived to when splashing into eye drop, the tear film on eye drop and eye surface particularly with the tear film in mucin contact this fact, through the discovery of concentrating on studies, the eye drop that contains the ophthalmic thickening agent that combines by hydroxyethyl-cellulose and glucosan, can bring into play the collaborative tackify effect of specificity when coexisting, thereby finish the present invention with mucin.In addition, the result that irregular index variation is tested according to anterior corneal surface described later as can be known, the eye drop that contains ophthalmic thickening agent of the present invention, owing to have excellent tear film stabilization effect, so can be used as dry eye treatment agent or artificial tears, ophthalmic thickening agent of the present invention in addition can also be as the good eye drop of comfort or to the base of the non-stimulated collyrium of eyes.
The eye drop that contains ophthalmic thickening agent of the present invention, the collaborative tackify effect of performance specificity when coexisting with mucin infers that this effect is to obtain with surperficial mucinous combination of eye by the ophthalmic thickening agent that promotes to be obtained by hydroxyethyl-cellulose and glucosan combination.When using ophthalmic thickening agent of the present invention as the base of eye drop, from the result of eye drop eye surface detention evaluation test described later as can be known, owing to have the effect of excellent raising eye drop anelasticity on the eye surface, therefore also can be applied to improve the drug delivery system (Drug Delivery System) of the anelasticity or the dividing a word with a hyphen at the end of a line property of ophthalmic of medicine pro-eye.
That is, the present invention relates to following content:
(1) a kind of ophthalmic thickening agent that combines by hydroxyethyl-cellulose and glucosan;
(2) a kind of eye drop, described eye drop contains the ophthalmic thickening agent that is combined by hydroxyethyl-cellulose and glucosan;
(3) pH is aforementioned (2) described eye drop of 4～8;
(4) as described above (2) described eye drop, wherein, the concentration of described hydroxyethyl-cellulose is 0.001～10% (w/v), and the concentration of described glucosan is 0.001～10% (w/v);
(5) as described above (2) described eye drop, wherein, the pH of described eye drop is 4～8, the concentration of described hydroxyethyl-cellulose is 0.001～10% (w/v), and the concentration of described glucosan is 0.001～10% (w/v);
(6) a kind of thickening agent, described thickening agent is combined by hydroxyethyl-cellulose and glucosan, it is characterized by, and has viscosity increase under the mucinous condition;
(7) a kind of eye drop, described eye drop contains the ophthalmic thickening agent that is combined by hydroxyethyl-cellulose and glucosan, it is characterized by, and contacts with the mucin of tear film during by eye drip viscosity is increased;
(8) a kind of tear membrane stabilizer that combines by hydroxyethyl-cellulose and glucosan;
(9) a kind of by splash into eye drop stablize the eye surperficial tear film system, wherein said eye drop contains the tear membrane stabilizer that is combined by hydroxyethyl-cellulose and glucosan;
(10) a kind of eye drop eye surface detention promoter that combines by hydroxyethyl-cellulose and glucosan;
(11) a kind ofly improve the system of the anelasticity of medicine pro-eye by splashing into eye drop, wherein said eye drop contains the eye drop eye surface detention promoter that is combined by hydroxyethyl-cellulose and glucosan;
(12) a kind of Therapeutic Method of ophthalmic, described Therapeutic Method be to the eye drop that contains hydroxyethyl-cellulose and glucosan of the effective therapeutic dose of patient;
(13) a kind of by splashing into the eye drop that contains hydroxyethyl-cellulose and glucosan to the patient, the method for the surperficial tear film of stable eye;
(14) a kind of by splash into the eye drop that contains hydroxyethyl-cellulose and glucosan to the patient, improve the method for the anelasticity of medicine pro-eye.
The eye drop that contains the ophthalmic thickening agent that combines by hydroxyethyl-cellulose and glucosan of the present invention, owing to can bring into play the collaborative tackify effect of specificity under the mucinous condition existing, so contact with mucin in the tear film when the eye drip, viscosity is increased, thereby continue performance desired drug effect or refrigerant sense.In addition, eye drop of the present invention can be stablized the tear film, therefore also can be used for eliminating the dry sensation or the sense of discomfort of eye, can also improve the xerophthalmia symptom.In aftermentioned " the viscosimetric analysis test when coexisting " item, elaborate with mucin, the thickening agent that hydroxyethyl-cellulose and glucosan are combined to form shows the collaborative tackify effect of specificity in the presence of mucinous, relative with it, the material that obtains as the hydroxypropyl emthylcellulose of other cellulose family adhesion agents and glucosan combination does not show collaborative tackify effect, shows that this effect is based on the specific physique of hydroxyethyl-cellulose.
In the thickening agent that combines by hydroxyethyl-cellulose and glucosan of the present invention, tear membrane stabilizer and eye drop eye surface detention promoter, the weight ratio of hydroxyethyl-cellulose and glucosan, preferably with respect to 0.001～10 hydroxyethyl-cellulose, glucosan is 0.001～10, more preferably with respect to 0.01～5 hydroxyethyl-cellulose, glucosan is 0.005～3.
The hydroxyethyl-cellulose that uses among the present invention is a cellulose family macromolecule, and various viscosity are arranged, and can select any one for use.The concentration of hydroxyethyl-cellulose does not have special restriction in the eye drop, but considers that from viewpoints such as the characteristic of eye drop or effects the concentration of hydroxyethyl-cellulose is 0.001～10% (w/v), more preferably 0.01～5% (w/v).
The glucosan that uses among the present invention is the polysaccharide that obtains of fermentation sucrose, and various mean molecule quantities are arranged, and can select any one for use.For example preferred Gentran 40 (mean molecule quantity about 40,000), macrodex (mean molecule quantity about 70,000).The concentration of glucosan does not have special restriction in the eye drop, but considers that from viewpoints such as the characteristic of eye drop or effects the concentration of glucosan is 0.001～10% (w/v), more preferably 0.005～3% (w/v).
Contain the eye drop of the ophthalmic thickening agent that combines by hydroxyethyl-cellulose and glucosan of the present invention, tear membrane stabilizer, eye drop eye surface detention promoter, can adopt general technology to carry out preparation, more preferably make eye drop preparation.
Can in eye drop of the present invention, cooperate medicine.Can enumerate antibacterial, antiinflammatory, hydryllin, antiglaucoma agent, anti-allergic agent, immunosuppressant, metabolic antagonist etc. as medicine.
Can suitably cooperate isotonic agent, buffer agent, pH regulator agent, solubilizing agent (solubilizing agent), stabilizing agent, preservative agent etc. in the eye drop of the present invention.
As isotonic agent, for example can enumerate glycerol, propylene glycol, sodium chloride, potassium chloride, sorbitol, mannitol etc.
As buffer agent, for example can enumerate phosphoric acid, citric acid, acetic acid, episilon amino caproic acid, boric acid, Borax, trometamol (Trometamol) etc.
As the pH regulator agent, for example can enumerate hydrochloric acid, citric acid, phosphoric acid, acetic acid, sodium hydroxide, potassium hydroxide, boric acid, Borax, sodium carbonate, sodium bicarbonate etc.
Be insoluble at medicine or other additives under the situation such as water,, for example can enumerate polysorbate 80, polyoxyethylene hardened castor oil 60, Macrogol 4000 etc. as the solubilizing agent of adding.
As stabilizing agent, for example can enumerate ethylenediaminetetraacetic acid (editic acid), sodium ethylene diamine tetracetate etc.
As preservative agent, can enumerate sorbic acid, potassium sorbate, benzalkonium chloride, benzethonium chloride (Benzethonium Chloride), methyl parahydroxybenzoate, propyl p-hydroxybenzoate, methaform etc., the use also capable of being combined of above-mentioned preservative agent.
Eye drop of the present invention preferably is set at 4.0～8.0 with pH, in addition, preferably the osmotic pressure ratio is set at about 1.0.
The eye drip number of times of eye drop of the present invention can suitably be selected according to symptom, age, dosage form etc., and dropped in eyes was about 1 time～6 times on 1st.
Elaborate in the viscosimetric analysis test when the coexistence of described later and mucin, contain the eye drop of the ophthalmic thickening agent that combines by hydroxyethyl-cellulose and glucosan of the present invention, show when coexist that specificity works in coordination with viscosifying action with mucin.So eye drop of the present invention contacts with mucin in the tear film during by eye drip, eye drop increases in the eye surface viscosity, can continue to bring into play desired drug effect or refrigerant sense etc.In addition, the result of the irregular index variation test of surface detention evaluation test of eye drop eye and anterior corneal surface shows, the eye drop that contains ophthalmic thickening agent of the present invention, because the anelasticity of medicine pro-eye is excellent and have an effect of stable tear film, can eliminate the dry sensation of eye, therefore can be used as eye drop eye surface detention promoter, tear membrane stabilizer, dry eye treatment agent or artificial tears, be used to eliminate eye dryness sense or sense of discomfort, can also be as the eye drop of comfort excellence or to the base of the non-stimulated collyrium of eyes.
Description of drawings
[Fig. 1] Fig. 1 represent to use be subjected to test solution 1, the fluorescence intensity survival rate of eye surface (tear film) and the figure of time relation when being subjected to test solution 6.
The specific embodiment
Below, enumerate embodiment and describe the present invention in detail, but this embodiment just is used for understanding better the present invention, can not limit scope of the present invention.
Viscosimetric analysis test during [1] with the mucin coexistence
This experimental evidence Pharmaceutical Research, 491-495, Vol.7, No.5, the test method of record in 1990, the viscosity when respectively being subjected to test solution and the coexistence of mucin solution by measuring is estimated the collaborative viscosifying action when contacted with mucin solution by test solution.
(experimental technique)
Press shown in the table 1 preparing normal saline and each thickening agent is dissolved in obtain being subjected to test solution 1～6 in the normal saline.In addition, mucin (SIGMA society system) is dissolved in the phosphate buffer of 0.1M, makes pH value identical, prepare 4% mucin solution (pH7.0) with tear (neutrality).
[table 1]
| Thickening agent (%) | |
| Be subjected to test solution 1 | Normal saline (contrast) |
| Be subjected to test solution 2 | Hydroxyethyl-cellulose (0.2) |
| Be subjected to test solution 3 | Hydroxypropyl emthylcellulose (0.25) |
| Be subjected to test solution 4 | Glucosan (0.1) |
| Be subjected to | Hydroxypropyl emthylcellulose (0.25)+glucosan (0.1) |
| Be subjected to test solution 6 | Hydroxyethyl-cellulose (0.2)+glucosan (0.1) |
Next, use rotating cylinder viscometer (Rheostress RS100 HAAKE society system), measure following each solution sliding speed in 2.5 minutes and be elevated to 150S from 0.1
-1The time 100S
-1Viscosity (η 1, η 2 and η 3), described solution for respectively be subjected to the mixed solution of test solution (2ml) and 4% mucin solution (6ml), respectively be subjected to test solution (2ml) and 0.1M phosphate buffer (6ml) mixed solution, reach the mixed solution of water (2ml) and 4% mucin solution (6ml).
η 1: the viscosity that respectively is subjected to the mixed solution of test solution (2ml) and 4% mucin solution (6ml)
η 2: the viscosity that respectively is subjected to the mixed solution of test solution (2ml) and 0.1M phosphate buffer (6ml)
η 3: the viscosity (result) of the mixed solution of water (2ml) and 4% mucin solution (6ml)
According to following formula, calculate the viscosity climbing of each mixed solution.Its result is as shown in table 2.
Viscosity climbing=(η 1-η 2-η 3)/η 2 * 100
Need to prove that when η 1 was identical with η 2 and η 3 degree, promptly almost during no change, the viscosity climbing that calculates according to following formula was about-100% to viscosity.In addition, when η 1 compares remarkable increase with η 2 and η 3, promptly during the collaborative tackify of η 1, the viscosity climbing that calculates according to following formula on the occasion of.
[table 2]
| Be subjected to test solution | Viscosity climbing (%) |
| Be subjected to test solution 1 | -105 |
| Be subjected to test solution 2 | -31 |
| Be subjected to test solution 3 | -21 |
| Be subjected to test solution 4 | -93 |
| Be subjected to test solution 5 | -47 |
| Be subjected to test solution 6 | +22 |
(discussion)
Under the thickening agent that hydroxyethyl-cellulose and glucosan combination obtain and the situation of mucin coexistence, show the collaborative viscosifying action (being subjected to test solution 6) of specificity.But, normal saline, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, glucosan do not have the collaborative viscosifying action (being subjected to test solution 1～4) of specificity when coexisting with mucin respectively, also show collaborative viscosifying action (being subjected to test solution 5) when in addition, the mixture of hydroxypropyl emthylcellulose and glucosan and mucin coexist.
[2] the irregular index variation test of anterior corneal surface
The cornea shape determinator is adopted in this test, splashes into the degree of irregularity (degree of irregularity of tear film) that is subjected to the test solution posterior corneal surface by mensuration, estimates respectively to be subjected to the Stabilization of test solution to the tear film.
(experimental technique)
Male Japanese white rabbit is splashing in eye respectively under the state of general anesthesia after 20 μ l are subjected to test solution 1, are subjected to test solution 6, mandatoryly uses cornea shape determinator (the system TMS-2N of TOMEY society) to measure 0 (just behind the eye drip), the anterior corneal surface shape after 10 minutes after opening eyelid.
(result)
(shape of the tear film of anterior corneal surface is irregular more according to the irregular index of measuring of sphere, the irregular exponential value of sphere is big more), calculate the irregular index variation of sphere (the irregular index of the sphere after 10 minutes deducts the value of the irregular index gained of sphere behind the firm eye drip).Its result is as shown in table 3.Need to prove that the irregular index variation of sphere that respectively is subjected to test solution is the meansigma methods of 3 examples or 5 examples.
[table 3]
| Be subjected to test solution | The irregular index variation of sphere after 10 minutes |
| Be subjected to test solution 1 | 0.81 |
| Be subjected to test solution 6 | 0.37 |
(discussion)
Table 3 shows, contain combination have hydroxyethyl-cellulose and glucosan thickening agent be subjected to test solution 6, compare with normal saline (being subjected to test solution 1), show significant tear film stablizing effect.
[3] eye drop eye surface detention evaluation test
This test is measured by eye fluorescence determination device before adopting and is splashed into the fluorescence intensity of being tried tear film behind the eye drop, estimates the eye surface detention effect that is respectively tried eye drop.
(experimental technique)
Male Japanese white rabbit is splashing in eye respectively under the state of general anesthesia after 20 μ l contain being subjected to test solution 1, being subjected to test solution 6 of 0.002% fluorescein sodium, the mandatory eyelid of opening, eye fluorescence determination device (Xinghe before adopting, FL-500), (just behind the eye drip) measured the fluorescence intensity of a tear film to 5 minutes the time in per 5 minutes to 30 minutes after per 1 minute, 10 minutes to 10 minutes after per 30 seconds, 5 minutes 0.
(result)
According to the fluorescence intensity of the tear film of measuring, calculate the meansigma methods (respectively 4 examples is average) of fluorescence intensity survival rate (is the ratio of the fluorescence intensity of 100% o'clock each minute with the fluorescence intensity behind the firm eye drip).Re-use the meansigma methods that calculates, carry out non-compartment analysis, calculating from behind the firm eye drip to 2 minutes λ z (expression disappearance speed, be worth more little anelasticity high more) and from behind the firm eye drip to 30 minutes AUC (represent area under fluorescence intensity-time graph, be worth big more anelasticity high more).The fluorescent strength determining result as shown in Figure 1, analysis result is as shown in table 4.
[table 4]
| Eye drop | λz 0-2 | AUC 0-30 |
| Be subjected to test solution 1 | 0.6194 | 431.3 |
| Be subjected to test solution 6 | 0.4639 | 611.7 |
(discussion)
Fig. 1 and table 4 show, what contain the thickening agent that obtained by hydroxyethyl-cellulose and glucosan combination is subjected to test solution 6, compares with normal saline (being subjected to test solution 1), shows a higher surface detention.
[formulation example]
Shown in the representative formulation of the ophthalmic thickening agent that cooperation is combined by hydroxyethyl-cellulose and glucosan is for example following.
Prescription example 1 (eye drop)
Among the 100ml
Hydroxyethyl-cellulose 500mg
Glucosan 300mg
The sodium dihydrogen phosphate dihydrate is an amount of
The 1N sodium hydroxide is an amount of
Hydrochloric acid is an amount of
Sterile purified water is an amount of
Identical with above-mentioned prescription example, prepare the eye drop that contains 100mg, 1g, 3g, 5g hydroxyethyl-cellulose among the 100ml.
Prescription example 2 (eye drop)
Among the 100ml
Hydroxyethyl-cellulose 300mg
Glucosan 300mg
The sodium dihydrogen phosphate dihydrate is an amount of
The 1N sodium hydroxide is an amount of
Hydrochloric acid is an amount of
Sterile purified water is an amount of
Identical with above-mentioned prescription example, prepare the eye drop that contains 50mg, 100mg, 500mg, 1g glucosan among the 100ml.
Claims (14)
1, a kind of ophthalmic thickening agent is combined by hydroxyethyl-cellulose and glucosan.
2, a kind of eye drop contains the ophthalmic thickening agent that is combined by hydroxyethyl-cellulose and glucosan.
3, eye drop as claimed in claim 2, wherein, the pH of described eye drop is 4～8.
4, eye drop as claimed in claim 2, wherein, the concentration of described hydroxyethyl-cellulose is 0.001～10% (w/v), and the concentration of described glucosan is 0.001～10% (w/v).
5, eye drop as claimed in claim 2, wherein, the pH of described eye drop is 4～8, the concentration of described hydroxyethyl-cellulose is 0.001～10% (w/v), and the concentration of described glucosan is 0.001～10% (w/v).
6, a kind of thickening agent, described thickening agent is combined by hydroxyethyl-cellulose and glucosan, it is characterized by, and viscosity increases in the presence of mucin.
7, a kind of eye drop, described eye drop contains the ophthalmic thickening agent that is combined by hydroxyethyl-cellulose and glucosan, it is characterized by, and contacts by the mucin with the tear film during eye drip viscosity is increased.
8, a kind of tear membrane stabilizer is combined by hydroxyethyl-cellulose and glucosan.
9, a kind of system of tear film of stable surface, this system stablizes the tear film on eye surface by splashing into eye drop, and described eye drop contains the tear membrane stabilizer that is combined by hydroxyethyl-cellulose and glucosan.
10, a kind of eye drop eye surface detention promoter is combined by hydroxyethyl-cellulose and glucosan.
11, a kind of system that improves the anelasticity of medicine pro-eye, this system improves the anelasticity of medicine pro-eye by splashing into eye drop, and described eye drop contains the eye drop eye surface detention promoter that is combined by hydroxyethyl-cellulose and glucosan.
12, a kind of Therapeutic Method of ophthalmic, described Therapeutic Method be to the eye drop that contains hydroxyethyl-cellulose and glucosan of the effective therapeutic dose of patient.
13, a kind of method of tear film of stable surface, this method is stablized the tear film on eye surface by splash into the eye drop that contains hydroxyethyl-cellulose and glucosan to the patient.
14, a kind of method that improves the anelasticity of medicine pro-eye, this method is by splashing into the anelasticity that the eye drop that contains hydroxyethyl-cellulose and glucosan improves medicine pro-eye to the patient.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP157574/2004 | 2004-05-27 | ||
| JP2004157574 | 2004-05-27 | ||
| JP248586/2004 | 2004-08-27 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102614112A Division CN102274172A (en) | 2004-05-27 | 2005-05-27 | Eye-drops |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1956737A true CN1956737A (en) | 2007-05-02 |
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ID=38063664
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200580016815.8A Pending CN1956737A (en) | 2004-05-27 | 2005-05-27 | Ophthalmic thickening agent |
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| Country | Link |
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| CN (1) | CN1956737A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113518646A (en) * | 2019-02-27 | 2021-10-19 | 参天制药株式会社 | Ophthalmic composition containing diquafosol or salt thereof, vinyl polymer and cellulose polymer |
-
2005
- 2005-05-27 CN CN200580016815.8A patent/CN1956737A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113518646A (en) * | 2019-02-27 | 2021-10-19 | 参天制药株式会社 | Ophthalmic composition containing diquafosol or salt thereof, vinyl polymer and cellulose polymer |
| CN113518646B (en) * | 2019-02-27 | 2023-12-12 | 参天制药株式会社 | Ophthalmic composition containing diquafosol or salt thereof, vinyl polymer and cellulose polymer |
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Open date: 20070502 |